Selective aortic arch perfusion with hemoglobin-based oxygen carrier-201 for resuscitation from exsanguinating cardiac arrest in swine.

OBJECTIVE: The prospects for resuscitation after blunt traumatic cardiac arrest are dismal. Selective aortic arch perfusion (SAAP) with a hemoglobin-based oxygen carrier (HBOC-201) offers a potentially effective therapy. This study evaluated the acute cardiovascular and metabolic effects of SAAP with HBOC-201 in an exsanguination model of cardiac arrest. DESIGN: Randomized, controlled, laboratory investigation. SETTING: University research laboratory. SUBJECTS: Domestic swine, 25-39 kg. INTERVENTIONS: Partial resection of four liver lobes rapidly led to profound hemorrhagic shock and subsequent cardiac arrest at 10-13 mins. At 15 mins, swine were randomized to receive either SAAP with oxygenated lactated Ringer's (LR) solution (n = 6) or SAAP with oxygenated HBOC-201 (n = 6) at a rate of 10 mL x kg(-1) x min(-1) until return of spontaneous circulation with a mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved. Epinephrine (0.005 mg/kg) was given via intra-aortic route every 30 secs as needed to promote return of spontaneous circulation beginning at 18 mins after onset of liver injury (3 mins after beginning SAAP). MEASUREMENTS AND MAIN RESULTS: Mean aortic pressure, cardiac output, total blood loss, and time of arrest were similar for both groups before SAAP therapy. In the SAAP-HBOC group, return of spontaneous circulation with a sustained mean aortic pressure of 60 mm Hg (8.0 kPa) was achieved in six of six swine at 1.9 +/- 0.3 mins of SAAP, and none of these swine required epinephrine. In the SAAP-LR group, no swine (from a total of six) achieved return of spontaneous circulation before intra-aortic epinephrine administration, and only two of six swine had brief return of spontaneous circulation with an mean aortic pressure of 60 mm Hg (8.0 kPa) after intra-aortic epinephrine that was sustained for <10 mins. One-hour survival was five of six in the SAAP-HBOC group and none of six in the SAAP-LR group (p <.05, Fisher's exact test). CONCLUSION: SAAP with oxygenated HBOC-201 rapidly restored viable cardiovascular function after exsanguinating cardiac arrest in this swine model of liver injury with profound hemorrhagic shock.

Effect of rates of perfusion on dominant frequency and defibrillation energy in isolated fibrillating hearts.

This study assessed the influence of rates of reperfusion on excitability of the myocardium using dominant frequency (DF) (in Hz) of VF and the relationship of DF to the minimum defibrillation energy (MDE) (in J). Our hypothesis was that increasing flow during reperfusion increases DF that raises MDE. Initially, six Langendorff perfused swine hearts were serially fibrillated and perfusion arrested for 4 minutes followed by reperfusion and defibrillation to establish reproducibility of the model. The epicardial ECG was analyzed for DF. In subsequent studies (n = 8), no flow VF was followed by 1-minute reperfusion at normal flow or 10% flow (low flow) and shocked with increasing energy via epicardial pads until defibrillation. The DF at onset of no flow VF was 9.5 +/- 1.4 and decreased to 3.6 +/- 1.4 after 4 minutes. Reperfusion at normal flow increased the DF of VF compared to low flow after 1 minute (10.8 +/- 1.1 vs 4.5 +/- 1.1 Hz, P = 0.0002) and was associated with increased defibrillation energy requirements (13.5 +/- 5.0 vs 7.3 +/- 6.2 J, P = 0.047). In summary, defibrillation energy requirements are lower when myocardial excitability is reduced during low flow reperfusion.

Selective aortic arch perfusion using serial infusions of perflubron emulsion.

OBJECTIVE: To determine whether selective aortic arch perfusion (SAAP) using serial infusions of oxygenated perflubron emulsion combined with aortic epinephrine (AoE) administration is more effective than conventional therapy in treating cardiac arrest. METHODS: An experimental cardiac arrest model (10 min ventricular fibrillation and 2 min CPR) was used with 12 mixed-breed canines, randomized into 2 groups: control (n = 6), CPR and IV epinephrine, 0.01 mg/kg, at 12 min and then every 3 min; or AoE-SAAP (n = 6), CPR and aortic epinephrine, 0.01 mg/kg, at 12 min and then every 3 min, and serial SAAP with oxygenated 60% weight/volume (w/v) perflubron emulsion as follows: 300 mL over 30 sec at 12 min as continuous SAAP without CPR; 150 mL over 20-30 sec at 15 min and 18 min as pulsed diastolic SAAP during CPR. RESULTS: AoE-SAAP resulted in increased coronary perfusion pressure (CPP) and return of spontaneous circulation (ROSC) compared with control. CPR-diastolic (release phase) CPP during pulsed diastolic SAAP was similar to or greater in magnitude than the CPP generated during the initial SAAP infusion without CPR. ROSC for control was 0/6 and for AoE-SAAP was 4/6 (p < 0.05, Fisher's exact test). Time from initiation of CPR to ROSC with a sustained systolic aortic pressure > 60 mm Hg was 8.0 +/- 1.2 min in the 4 resuscitated AoE-SAAP animals. CONCLUSION: The combination of AoE with SAAP infusions of oxygenated perflubron emulsion was more effective than conventional resuscitation therapy. Pulsed diastolic SAAP is a promising method for performing SAAP.

Selective aortic arch perfusion during cardiac arrest: enhanced resuscitation using oxygenated perflubron emulsion, with and without aortic arch epinephrine.

STUDY OBJECTIVE: To evaluate selective aortic arch perfusion (SAAP) with an oxygenated fluorocarbon emulsion, with and without aortic arch epinephrine during cardiac arrest. METHODS: This randomized, controlled study, undertaken at a university research laboratory, involved 15 mixed-breed dogs. After 10 minutes of ventricular fibrillation and 30 seconds of CPR, the dogs were randomized to three groups, each comprising five dogs. Group 1 (controls) dogs were given CPR and intravenous epinephrine, .01 mg/kg, at 10.5 minutes and then every 3 minutes. Group 2 dogs (IVE-SAAP) were treated with CPR and intravenous epinephrine (IVE) in the same fashion as the control group but were also subjected to SAAP with 275 mL of oxygenated 60% wt/vol perflubron emulsion over 30 seconds. Group 3 dogs (AoE-SAAP) received the same treatment as the IVE-SAAP group, except that the first epinephrine dose was given intraaortically. RESULTS: Coronary perfusion pressure (CPP) increased during SAAP in both the IVE-SAAP and AoE-SAAP groups but was greater in the AoE-SAAP group. CPR diastolic CPP after SAAP was significantly greater in the AoE-SAAP group than in the control group. Return of spontaneous circulation (ROSC) occurred in two control dogs, all five IVE-SAAP dogs, and all five AoE-SAAP dogs. The time elapsed from the initiation of CPR to ROSC was 6.1 +/- 1.9 minutes in the AoE-SAAP group, compared with 11.0 +/- 5.8 minutes in the IVE-SAAP group. CONCLUSION: SAAP with oxygenated perflubron emulsion improved ROSC, both with and without aortic arch epinephrine. The combination of SAAP with perflubron emulsion and aortic arch epinephrine resulted in higher CPP and more rapid ROSC.

Aortic arch versus central venous epinephrine during CPR.

STUDY OBJECTIVE: To determine if delivery of epinephrine to the peripheral arterial system by an aortic arch catheter is more effective than central venous epinephrine administration during cardiac resuscitation. DESIGN: Randomized, nonblinded, controlled trial. TYPE OF PARTICIPANTS: Sixteen mongrel canines (25 to 31 kg). INTERVENTIONS: Animals had aortic arch pressure, and right atrial pressure, superior vena cava infusion, and descending aortic arch infusion catheters placed using fluoroscopy. After ten minutes of ventricular fibrillation, three DC countershocks were delivered over one minute. If unsuccessful, CPR at 120 compressions per minute was begun, and at 60 seconds of CPR, epinephrine (1 mg/50 mL normal saline) was administered either through the superior vena cava or the aortic arch catheter followed by one more minute of CPR. Defibrillation then was attempted and, if unsuccessful, further resuscitative efforts followed advanced cardiac life support guidelines, except route and dose of epinephrine remained the same. MEASUREMENTS AND MAIN RESULTS: Aortic arch pressure, right atrial pressure, and coronary perfusion pressure (diastolic aortic arch pressure minus diastolic right atrial pressure) were recorded continuously. Aortic arch pressure and coronary perfusion pressure increased more rapidly and to a greater magnitude with aortic arch-epinephrine than superior vena cava-epinephrine. Coronary perfusion pressure doubled by ten seconds in seven of eight in the aortic arch-epinephrine group versus none in the superior vena cava-epinephrine group. Aortic arch pressure and coronary perfusion pressure increases consistently plateaued within 60 seconds after aortic arch-epinephrine but not after superior vena cava-epinephrine. Return of spontaneous circulation was faster (P < .05) in the aortic arch-epinephrine group. Maximal coronary perfusion pressure after epinephrine correlated with the coronary perfusion pressure immediately before epinephrine administration in both groups, but more strongly in the aortic arch-epinephrine group (P = .0001). CONCLUSION: For an equivalent dose of epinephrine, aortic arch administration produces a more rapid response and more rapid peak effect than central venous administration. The combination of aortic arch-epinephrine administration and aortic pressure monitoring may be useful when initial standard resuscitative measures have not been successful.